Distensible dilatation balloon with elastic stress response and manufacture thereof

ABSTRACT

Balloons and balloon catheters with a superior overall combination of distensibility, elastic stress response and strength. The improved properties of the balloons result from the method or process used to form the balloons, as well as the polymeric materials used in said balloon forming process. Additionally, the enhanced combination of properties of the balloons will not be adversely affected by the novel sterilization process contemplated by this invention.

BACKGROUND OF INVENTION

[0001] Surgical procedures employing balloons and medical devicesincorporating those balloons (i.e., balloon catheters) are becoming morecommon and routine. These procedures, such as angioplasty procedures,are conducted when it becomes necessary to expand or open narrow orobstructed openings in blood vessels and other passageways in the bodyto increase the flow through the obstructed areas. For example, in anangioplasty procedure, a dilatation balloon catheter is used to enlargeor open an occluded blood vessel which is partially restricted orobstructed due to the existence of a hardened stenosis or buildup withinthe vessel. This procedure requires that a balloon catheter be insertedinto the patient's body and positioned within the vessel so that theballoon, when inflated, will dilate the site of the obstruction orstenosis so that the obstruction or stenosis is minimized, therebyresulting in increased blood flow through the vessel. Often, however, astenosis requires treatment with multiple balloon inflations.Additionally, many times there are multiple stenoses within the samevessel or artery. Such conditions require that either the samedilatation balloon must be subjected to repeated inflations, or thatmultiple dilatation balloons must be used to treat an individualstenosis or the multiple stenoses within the same vessel or artery.Additionally, balloons and medical devices incorporating those balloonsmay also be used to administer drugs to a patient.

[0002] Traditionally, the balloons available to physicians wereclassified as either “compliant” or “noncompliant”. This classificationis based upon the operating characteristics of the individual balloon,which in turn depended upon the process used in forming the balloon, aswell as the material used in the balloon forming process. Both types ofballoons provide advantageous qualities which were not available fromthe other.

[0003] A balloon which is classified as “noncompliant” is characterizedby the balloon's inability to grow or expand appreciably beyond itsrated or nominal diameter. “Noncompliant” balloons are referred to ashaving minimal distensibility. In balloons currently known in the art(e.g., polyethylene terephthalate), this minimal distensibility resultsfrom the strength and rigidity of the molecular chains which make up thebase polymer, as well as the orientation and structure of those chainsresulting from the balloon formation process. The strength resultingfrom this highly oriented structure is so great that when the balloon issubjected typical inflation or operating pressures (i.e., about 70 psito over 200 psi), it will not be stressed above the yield point of thepolymeric material.

[0004] The yield point of a material is defined as the stress at whichthe individual molecular chains move in relation to one another suchthat when the pressure or stress is relieved, there is permanentdeformation of the structure. When a material is subjected to pressureor stress below its yield point, the material will consistently followthe same stress-strain curve when subjected to multiple cycles ofapplying and relieving the stress or pressure. A material which exhibitsthe ability to follow the same stress-strain curve during the repeatedapplication and relief of stress is defined as being elastic and ashaving a high degree of elastic stress response. This elastic behavioris highly desirable in balloons in order to ensure consistent andpredictable balloon sizing regardless of the balloon's previousinflation history.

[0005] A balloon which is referred to as being “compliant” ischaracterized by the balloon's ability to grow or expand beyond itsnominal or rated diameter. In balloons currently known in the art (i.e.,polyethylene, polyvinylchloride), the balloon's “compliant” nature ordistensibility results from the chemical structure of the polymericmaterial used in the formation of the balloon, as well as the balloonforming process. These polymeric materials have a relatively low yieldpoint. Thus, the inflation pressures used in dilation procedures aretypically above the yield point of the materials used to formdistensible balloons. A distensible or “compliant” balloon when inflatedto normal operating pressures, which are greater than the polymericmaterial's yield point, is subjected to stress sufficient to permanentlyrealign the individual molecular chains of the polymeric material. Therealignment of individual polymer chains permits the balloon to expandbeyond its nominal or rated diameter. However, since this realignment ispermanent, the balloon will not follow its original stress-strain curveon subsequent inflation-deflation cycles. Therefore, the balloon balloonupon subsequent inflations, will achieve diameters which are greaterthan the diameters which were originally obtained at any given pressureduring the course of the balloon's initial inflation.

[0006] The term “elastic”, as it is used in connection with thisinvention, refers only to the ability of a material to follow the samestress-strain curve upon the multiple applications of stress. See Beer,F. et al., Mechanics of Materials (McGraw-Hill Book Company 1981), pp.39-40. Elasticity, however, is not necessarily a function of howdistensible a material is. It is possible to have an elastic,non-distensible material or a non-elastic, distensible material. This isbest illustrated in FIGS. 1, 2 and 3.

[0007]FIG. 1 represents an elastic, essentially non-distensiblematerial. If this material was used to form a balloon, the balloon wouldbe considered non-distensible because there is very little change instrain (diameter) as the stress applied is increased (inflationpressure). The balloon would be elastic because it follows essentiallythe same stress-strain (pressure-diameter) curve with the secondapplication of stress (inflation).

[0008]FIG. 2 represents an elastic, distensible material. If thismaterial was used to form a balloon, the balloon would be considereddistensible because there is significant change in strain (diameter) asthe stress applied is increased (inflation pressure). The balloon wouldbe considered elastic because it follows essentially the samestress-strain (pressure-diameter) curve with the second application ofstress (inflation).

[0009]FIG. 3 represents an inelastic, distensible material. Like FIG. 2,FIG. 3 shows a significant change in strain (diameter) and wouldtherefore be considered a distensible balloon material. Unlike FIGS. 1and 2, however, the same stress-strain (pressure-diameter) curve is notmaintained upon the second application of stress (inflation).

[0010] It has been found that the optimal size of a dilatation balloonis about 0.9 to about 1.3 the size of the vessel being treated. SeeNichols et al., Importance of Balloon Size in Coronary Angioplasty, J.American College of Cardiology, Vol. 13, 1094 (1989). If an undersizedballoon is used, there is a high incidence of significant residualstenosis and a greater need for subsequent dilatation procedures.However, if an oversized balloon is used, there is an increased chanceof coronary dissection. Therefore, physicians desire to use a balloonwhich will closely approximate the size of the occluded vessel orobstructed cavity being treated.

[0011] Because physiological vessels such as arteries are generallytapered, the nominal or rated diameter of balloons commerciallyavailable often do not correspond to the size of the vessel beingtreated. Physicians, therefore, are often faced with the prospect ofusing an undersized “compliant” balloon which can be expanded beyond itsnominal or rated diameter, or an oversized “noncompliant” balloon whichwill follow the same stress-strain curve during multiple inflations(i.e., is elastic). Thus, physicians can choose from two general typesof balloons depending upon whether they require a balloon which growsbeyond nominal diameter. They may choose a “noncompliant” balloon ifthey require a relatively high strength balloon which will not expandmuch beyond its nominal or rated diameter, or a “compliant” balloon ifthey require a balloon which is capable of expanding considerably beyondthe normal or rated diameter. As will be shown below, each of theseproperties is advantageous. However, it would be desirable to have tohave a “compliant” or distensible balloon which also has the elasticstress response of a “noncompliant” balloon, as well as sufficientstrength to be used in dilatation procedures.

[0012] Because physicians using a dilatation balloon do not know priorto the procedure what inflation pressures will be required to dilate agiven obstruction or stenosis, it is desirable that the balloon beingused have strength capable of withstanding the high inflation pressurestypically associated with these procedures (i.e., about 70 to over 200psi). A high strength dilatation balloon, which is capable ofwithstanding increased inflation pressure, is safer to use since thechances of the balloon bursting during the procedure are minimized.

[0013] Strength of a balloon is typically quantified by calculating theballoon's wall tensile strength. The overall strength of a balloon canbe increased by increasing the balloon's wall thickness. As the wallthickness is increased, the balloon is capable of withstanding higherinflation pressures. However, as the wall thickness of the balloon isincreased, the folded profile of the balloon, as well as the balloon'sflexibility, may be adversely affected.

[0014] The relationship between the ultimate strength of the balloon,the inflation pressure which the balloon can withstand and the balloon'swall thickness is determined by the well known membrane equation:${{Wall}\quad {Tensile}\quad {{Strength}({psi})}} = \frac{\left( {{burst}\quad {{pressure}({psi})}} \right) \times \left( {{nominal}\quad {balloon}\quad {diameter}} \right)}{2 \times \left( {{wall}\quad {thickness}} \right)}$

[0015] Depending upon the material used to form the balloon, thenominal, or rated diameter is achieved typically when the balloon isinflated between to about 5 bars to about 8 bars. The burst pressure isdetermined at 37° C.

[0016] Since balloons, particularly dilatation balloons, must have theability to traverse the confines of the obstructed areas to be treated,it is desirable to have a balloon which has a narrow folded profile.This “profile” represents the smallest opening through which theballoon, in its deflated state, may pass. The profile of the balloondepends in large part upon the wall thickness of the finished balloon(i.e., the sterilized dilatation balloon product). Therefore, it isdesirable for a finished balloon product to have a folded profile whichis as narrow as possible, particularly if the balloon is to be used inan angioplasty procedure.

[0017] Another important characteristic of balloons in general, and morespecifically dilatation balloons, is the distensibility of the finishedballoon product. Distensibility, also referred to as percent of radialexpansion, is typically determined by comparing the nominal or rateddiameter of the balloon with the diameter at some arbitrarily selectedhigher pressure (i.e., 10 bars). The distensibility or percent radialexpansion is calculated using the following formula with allmeasurements taking place at about 37° C.:${Distensibility} = {\left\lbrack {\frac{{Diameter}\quad {of}\quad {balloon}\quad {at}\quad 10\quad {bars}}{{Nominal}\quad {balloon}\quad {diameter}} - 1} \right\rbrack \times 100\quad \%}$

[0018] For example, balloons made of polyethylene terephthalate have alow distensibility (i.e., less than about 5% at 200 psi). See forexample U.S. Pat. Re. Nos. 32,983 and 33,561 to Levy which disclosesballoons formed from polyethylene terephthalate and other polymericmaterials.

[0019] It is also desirable that the balloon be elastic or have a highdegree of elastic stress response. Elasticity, which also can bereferred to as the repeatability of a balloon, is characterized by theability of the balloon to consistently follow the same stress-straincurve after being subjected to multiple inflations to normal operatingor inflation pressures (i.e., about 10 bars or greater). That is, aballoon which has a high degree of elastic stress response will retainthe same diameter-pressure relationship and will consistently obtain thesame diameter at the same pressure during repeated inflation-deflationcycles. Balloons which have poor elasticity or a low degree of elasticstress response have a tendency to “creep” or “deform” after multipleinflations and fail to return to their nominal or rated diameters afterbeing subjected to multiple inflations at increased pressures.

[0020] A dilatation balloon which has a high degree of elastic stressresponse is particularly desirable when a physician is treating multiplestenoses within the same artery. If the balloon is “inelastic”, afterthe first stenosis is dilated at an increased pressure, the physicianwould not know what the balloon's “new” starting diameter is prior toattempting to dilate subsequent stenoses. If the physician fails tocorrectly guess the balloon's “new” diameter prior to beginningtreatment of another stenosis there is an increased risk of oversizingthe balloon which could result in coronary artery dissection or otherdamage to the vessel. Therefore, to ensure the patient's safety, somephysicians elect to remove the balloon catheter from the patient andreintroduce a new sterile balloon catheter prior to attempting to dilatesubsequent stenosis within the same vessel. However, this istime-consuming and undesirable for the patient. Additionally, the costof the individual balloon catheters prohibits the use of multipleballoon catheters when treating multiple stenoses within the samevessel. Thus, to minimize the chance of oversizing the balloon whentreating multiple stenoses within the same vessel, a physician mayattempt to use a dilatation balloon which is noncompliant. However, asdiscussed previously, because such a balloon will permit littleexpansion beyond the balloon's rated or nominal diameter, the physicianmay not have available a balloon of sufficient size to safely treat theother stenoses within the same vessel.

[0021] Elastic stress response is determined by inflating a balloon to 5bars at about 37° C. and measuring the balloon's diameter. The balloonis then inflated to a pressure of 10 bars in about 20 seconds and heldfor an additional 20 seconds at 37° C. The balloon's diameter is thenmeasured. The internal pressure of the balloon is then decreased to 5bars and the “new” 5 bar diameter of the balloons is determined. Forthis invention, the elastic stress response or repeatability iscalculated using the following equation:${{Elastic}\quad {Stress}\quad {Response}} = {\quad{\left\lbrack {\frac{{Balloon}\quad {diameter}\quad {at}\quad 5\quad {bars}\quad {after}\quad {inflation}\quad {to}\quad 10\quad {bars}}{{Balloon}\quad {diameter}\quad {at}\quad {initial}\quad 5\quad {bar}\quad {inflation}} - 1} \right\rbrack \times 100}}$

[0022] A balloon with maximum or complete elastic stress responsepermits the balloon, after being inflated to a pressure of 10 bars, toreturn to the same diameter it had at 5 bars prior to the inflation tothe higher pressure. Such a balloon would have maximum repeatability, oran elastic stress response of 0.00. As the repeatability of the balloondecreases, the elastic stress response decreases and, as defined above,numerically becomes greater than 0.00. For example, balloons formed frompolyolefin copolymers in the art have poor repeatability and arelatively low degree of elastic stress response and have a numericalelastic stress response of about 9.

[0023] It would be particularly desirable if a “compliant” balloon wasable to possess an adequate degree of distensibility so that the ballooncould be inflated to correspond to the size of the vessel being treated,while at the same time being highly elastic to ensure repeatable sizingand a high degree of elastic stress response so that the physician wouldknow the balloon's “new” diameter at all inflation pressures prior toattempting to dilate multiple stenoses within the same vessel. Thisenhanced combination of properties would allow physicians to conductdilation procedures in a safer manner in arteries where the physicianrequires balloon sizing not conveniently provided by “noncompliant”balloon products currently available in the art.

[0024] Another desirable characteristic of a balloon is flexibility.Improved flexibility will permit a balloon to traverse, not onlyoccluded arteries, but also other obstructed or narrow body cavities andopenings resulting in minimal damage to the vessel or cavity throughwhich the balloon catheter is being navigated.

[0025] A further desirable property of a dilatation balloon, is theoptical clarity of the finished balloon product. Although the opticalclarity will not adversely affect a balloon's overall ability to dilatea stenosis or obstruction, most physicians will not use a balloon whichhas a cloudy appearance. The optical characteristics of a balloon orballoon catheter, therefore, must be taken into account when forming aballoon.

[0026] While the foregoing properties are desirable in balloons, theseattributes are typically adversely affected by the sterilization processwhich all balloons and balloon catheters must be subjected to prior totheir use in the human body. For example, when a balloon in the art isexposed to the increased temperature and humidity of a traditionalsterilization process (e.g., high humidity, temperature of about 50-60°C., about 12% ethylene oxide and about 88% Freon™ for approximately12-16 hours) the balloon tends to shrink which causes a correspondingincrease in wall thickness. Moreover, this increase in wall thicknesswill adversely affect the folded profile of the sterilized balloonproduct. Furthermore, the distensibility of many balloons is adverselyaffected by the sterilization processes currently used in the art.Therefore, it is also desirable that the sterilization process used totreat balloons and balloon catheters provide adequate sterilizationwhile at the same time not adversely affecting the physicalcharacteristics of the finished balloon or balloon catheter product.

[0027] It has now been found that novel distensible balloons,particularly dilatation balloons, can be formed by processing apolymeric material composed of polymer chains having sufficient regionsof molecular structure with inter-molecular chain interaction to ensurethe integrity and strength of the structure, as well as sufficientregions which permit sections of the polymer chains to “uncoil” topermit growth. The balloons contemplated by this invention (i) aresufficiently distensible (i.e., about 5 to about 20%) to allow treatmentof various sized arteries, (ii) have a high degree of elastic stressresponse (i.e., less than about 5.00) which permits the physician totreat multiple stenoses within the same artery without having to beconcerned with increasing balloon diameter after repeated inflations and(iii) have strength sufficient to treat hardened stenoses (i.e., greaterthan about 14,000 psi). The balloons formed using the process of thisinvention will have an overall advantageous combination of thesephysical properties i.e., distensibility, elastic stress response andtensile strength, superior to those exhibited by the “compliant”balloons currently available. It has also been found that these enhancedproperties will not be adversely affected by subjecting the balloons andballoon catheters formed following the method or process of thisinvention to a novel sterilization process. This novel balloon formingprocess and novel sterilization process can be used regardless ofwhether the balloon is coated.

SUMMARY OF THE INVENTION

[0028] It is an object of this invention to provide a method or processfor producing a balloon, preferably a dilatation balloon, which exhibitsan improved overall combination of physical properties, such asdistensibility, elastic stress response and strength, superior to thoseexhibited by “compliant” balloons currently known in the art.

[0029] It is further the object of this invention to provide a novelballoon and a novel balloon catheter in which the balloon exhibits anadvantageous overall combination of distensibility, elastic stressresponse and strength which combination of properties will not beadversely affected by sterilization.

[0030] Still another object of this invention is to provide an improvedsterilization procedure which will not adversely affect thedistensibility, elastic stress response and strength of the balloons andballoons of the balloon catheters of this invention.

[0031] It is still a further object of this invention to provide aprocess which will ensure that the balloons formed will have improvedoptical clarity.

[0032] These objects, as well as others, which will become apparent fromthe description which follows, are achieved by forming these novelballoons and balloon catheters using the novel process of this inventionfrom certain polymeric materials composed of polymer chains havingregions of inter-molecular chain interaction separated by regions inwhich those individual portions of the polymer chains have the abilityto uncoil or stretch. Therefore, the present invention includes (1)novel balloons and balloon catheters which have an improved overallcombination of distensibility, elastic stress response and strength, (2)the process or method of forming balloons and balloon catheters frompolymeric materials which will result in balloons and balloon cathetersexhibiting these improved properties and (3) a novel sterilizationprocess which will not adversely affect these enhanced properties.

[0033] The present invention contemplates balloons characterized by animproved overall combination of distensibility, elastic stress responseand wall tensile strength made by the process comprising subjecting aparison, made of a block copolymer having polymer chains with regions ofinter-molecular chain interaction separated by regions in which thoseindividual portions of the polymer chains have the ability to stretch oruncoil to at least one axial stretch and at least one radial expansionstep. The expanded parison is then subjected to a heat set step toprovide the expanded parison and resulting balloon with thermal anddimensional stability. The invention also contemplates a novelsterilization process in which balloons and balloon catheters, afterpreconditioning, are exposed to ethylene oxide at a temperature of about40° C. and a relative humidity of about 50-60% for approximately 6hours. The balloons and balloon catheters are then subjected to anaeration step in which the ethylene oxide is allowed to dissipate. Thenovel sterilization process does not adversely affect the improvedoverall combination of properties exhibited by the balloons of thisinvention.

[0034] It should be understood that the foregoing description of theinvention is intended merely to be illustrative and that otherembodiments and modifications may be apparent to those skilled in theart without departing from the spirit and scope of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0035] The present invention provides for the first time “compliant”balloons, preferably dilatation balloons, which, because of the methodor process used to form the balloons, as well as the polymeric materialsused in the balloon forming process, produces balloons having a highlydesirable combination of distensibility, elastic stress response andstrength (i.e., distensibility of about 5 to about 20% and preferably inthe range of about 6 to about 17%, elastic stress response of notgreater than about 5.00 and preferably in the range of about 0.75 toabout 4.00 and wall tensile strength of at least about 14,000 psi,preferably in the range of about 15,000 to about 40,000 psi and mostpreferably in the range of about 16,000 to about 30,000 psi). Theinvention also provides a unique method or process using a heat set stepin the formation of the balloons of this invention which ensures thatthe balloons retain their distensibility and strength, and providesballoons with improved optical clarity. Moreover, the invention providesa novel sterilization process which will not adversely affect, to anysignificant degree, the enhanced combination of properties which areobtained using the novel balloon forming process of this invention.

[0036] The materials which may be used in this novel process or methodinclude polymeric materials having a molecular structure which arecomposed of individual polymer chains having regions or zones ofinter-molecular chain interaction separated by regions or zones in whichthose individual portions of the polymer chains have the ability tostretch or uncoil. The ability of regions or zones of individual polymerchains to uncoil permits the chains to move upon the application ofstress. However because these zones are held in place or secured ateither end by zones exhibiting inter-molecular chain interaction, theuncoiled portions return to their original position once the appliedstress is removed.

[0037] These polymers can be considered to be comprised of polymerchains with individual regions of crystalline and amorphous material andcan be referred to as “hard” and “soft” segments respectively. Theindividual polymer chains are able, to a substantial extent, to coilupon themselves and/or around each other in such a way that softsegments are associated with soft segments and hard segments with hardsegments, thereby forming separate “domains” approximating soft and hardbodies of polymer, each exhibiting its own physical properties invarying degrees. The hard segments are comprised of regions which havesignificant inter-molecular chain interaction. This provides regionswith increased strength and increased elastic stress response. Inaddition to providing strength, the hard segments are sufficiently rigidto permit the soft segments to stretch and uncoil which providesdistensibility.

[0038] The ratio of hard to soft segments and individual chemicalstructure of the individual segments define the balloon'sdistensibility, elastic stress response and strength. Therefore, thepolymeric material used in accordance with this invention should havehard segments present in an amount sufficient to achieve a high degreeof elastic stress response (i.e., not greater than about 5.00) andadequate wall tensile strength (i.e., at least about 14,000 psi), whileat the same time having an adequate amount of soft segments to ensurethat the balloon is also distensible (i.e., about 5 to about 20%).

[0039] Examples of polymeric materials which have these alternatingzones or regions and which may be used in forming the balloons andballoon catheters of this invention include block copolymers, andphysical mixtures of different polymers. Examples of block copolymerswhich may be used include polyester block copolymers, polyamide blockcopolymers and polyurethane block copolymers. Examples of the mixtureswhich may be used include mixtures of nylon and polyamide blockcopolymers and polyethylene terephthalate and polyester blockcopolymers. The preferred block copolymer which can be used inaccordance with the process of this invention is polyurethane blockcopolymer. This preferred polymer may be made, for example, by areaction between

[0040] a) an organic diisocyanate;

[0041] b) a polyol; and

[0042] c) at least one chain extender.

[0043] The preferred polyurethanes which can be used in this inventionmay be varied by using different isocyanates and polyols which willresult in different ratios of hard to soft segments as well as differentchemical interactions within the individual regions of the polymer.

[0044] An example of the most preferred polyurethane is manufactured byThe Dow Chemical Company and marketed under the trade name PELLETHANE2363-75D. This raw material has a Shore Hardness of about 74 D, aspecific gravity of about 1.21, a tensile modulus of about 165,000 psi,a flexural modulus of about 190,000 psi, an ultimate tensile strength ofabout 6,980 psi and an ultimate elongation of about 250%.

[0045] In accordance with this invention, the balloons are formed from athin wall parison of a polymeric material, preferably made of apolyurethane block copolymer, which is treated in accordance with theprocess of this invention. The novel process contemplated by thisinvention employs a heat set step which will provide a balloon withtemperature and dimensional stability. This stability results from thefact that the balloon is heated above the temperature using in theballoon forming process so that the orientation resulting from theprocessing conditions is “locked” into position.

[0046] The balloons and balloon catheters of this invention may beformed using a mold which can be provided with a heating element. Themold receives a tubular parison made of a polymeric material of the typeused in accordance with the present invention. The ends of the parisonextend outwardly from the mold and one of the ends is sealed while theother end is affixed to a source of inflation fluid, typically nitrogengas, under pressure. Clamps or “grippers” are attached to both ends ofthe parison so that the parison can be drawn apart axially in order toaxially stretch the parison while at the same time said parison iscapable of being expanded radially or “blown” with the inflation fluid.The radial expansion and axial stretch step or steps may be conductedsimultaneously, or depending upon the polymeric material of which theparison is made, following whatever sequence is required to form aballoon. Failure to axial stretch the parison during the balloon formingprocess will result in result in a balloon which will have an unevenwall thickness and which will exhibit a wall tensile strength lower thanthe tensile strength obtained when the parison is both radially expandedand axially stretched.

[0047] The polymeric parisons used in this invention are preferablydrawn axially and expanded radially simultaneously within the mold. Toimprove the overall properties of the balloons formed, it is desirablethat the parison is axially stretched and blown at temperatures abovethe glass transition temperature of the polymeric material used. Thisexpansion usually takes place at a temperature between about 80 andabout 150° C. depending upon the polymeric material used in the process.

[0048] In accordance with this invention, based upon the polymericmaterial used, the parison is dimensioned with respect to the intendedfinal configuration of the balloon. It is particularly important thatthe parison have relatively thin walls. The wall thickness is consideredrelative to the inside diameter of the parison which has wallthickness-to-inside diameter ratios of less than 0.6 and, preferablybetween 0.57 and 0.09 or even lower. The use of a parison with such thinwalls enables the parison to be stretched radially to a greater and moreuniform degree because there is less stress gradient through the wallfrom the surface of the inside diameter to the surface of the outsidediameter. By utilizing a parison which has thin walls, there is lessdifference in the degree to which the inner and outer surfaces of thetubular parison are stretched.

[0049] The parison is drawn from a starting length L1 to a drawn lengthL2 which preferably is between about 1.10 to about 6 times the initiallength L1. The tubular parison, which has an initial internal diameterID1 and an outer diameter OD1 is expanded by the inflation fluid emittedunder pressure to the parison to an internal diameter ID2 which ispreferably about 6 to about 8 times the initial internal diameter ID1and an outer diameter OD2 which is about equal to or preferably greaterthan about 3 times the initial outer diameter OD1. The parison ispreferably subjected to between 1 and 5 cycles during which the parisonis axially stretched and radially expanded with an inflation pressure ofbetween about 100 and about 500 psi. Nitrogen gas is the preferableinflation fluid for the radial expansion step.

[0050] After the desired number of “blow” cycles have been completed,the expanded parison is subjected to a heat set or thermoforming stepduring which the expanded parison, still subjected to an inflationpressure of about 100 to about 500 psi, is held at a temperature abovethe temperature at which the balloon was axially stretched and radiallyexpanded, but below the melting temperature of the polymeric materialfrom which the parison was formed. This higher temperature inducescrystallization and “freezes” or “locks” the orientation of the polymerchains which resulted from axially stretching and radially expanding theparison. The temperatures which can be used in this heat set step aretherefore dependent upon the particular polymeric material used to formthe parison and the ultimate properties desired in the balloon product(i.e., distensibility, strength and compliancy). The heat set stepensures that the expanded parison and the resulting balloon will havetemperature and dimensional stability. After the heat set step iscompleted, the mold is cooled to about 37° C. The finished balloon willtypically obtain its rated or nominal diameter when inflated to apressure of about 5 to about 8 bars depending upon the polymericmaterial used to form the balloon. The balloon thus formed may beremoved from the mold, and affixed to a catheter.

[0051] For example, if the parison is formed from the polyurethanemarketed by The Dow Chemical Company under the trade name PELLETHANE2363-75D and axially stretched and radially expanded at a temperature ofabout 90-100° C., the heat set step would preferably be conducted atabout 105-120° C. If this step was conducted at temperatures much aboveabout 120° C., the tensile strength of the resulting polyurethaneballoon would decrease significantly. Moreover, if the heat set step wasconducted at temperatures significantly higher than 120° C., thedistensibility of the resulting polyurethane balloon would also beadversely affected. However, if the heat set was conducted attemperatures below about 100° C., the polyurethane balloons formed wouldbe dimensionally unstable resulting in balloons with uneven wallthicknesses. Additionally, the lower heat set temperature would resultin balloons exhibiting physical properties which would more likely beadversely affected during sterilization. Finally, a balloon having acloudy appearance, a property which physicians find particularlyundesirable, would be another consequence of using a low heat settemperature.

[0052] It should be noted that some adjustment in the foregoing axialstretch and radial expansion ratios, as well as the expansion and heatset temperatures may be necessary to take into account the difference inphysical properties between the polyurethane block copolymer exemplifiedabove and any other polymeric materials which can be used in accordancewith this invention.

[0053] In order to preserve a balloon's distensibility, elastic stressresponse, wall tensile strength and improved optical clarity, theballoon formed must also be subjected to the novel sterilization processcontemplated by the invention. For example, if a sterilization processwhich is currently available in the art is used (e.g., high relativehumidity at about 50-60° C. in the presence of about 12% ethylene oxideand about 88% Freon™ for about 9-16 hours), the elastic stress response,distensibility and the strength of the balloons contemplated by thisinvention would be adversely affected. When the novel low temperature,low humidity, ethylene oxide sterilization process of this invention isused to sterilize the balloons and balloon catheters of this invention,the elastic stress response, distensibility and strength of the balloonsare not adversely affected to any significant degree.

[0054] The novel low temperature, low humidity sterilization processconsists of exposing the balloon or balloon catheter to apreconditioning step at temperature about 35 to about 45° C. and arelative humidity of about 55% for about 15 hours. The balloon orballoon catheter is then treated at a temperature of about 35 to about45° C. and a relative humidity of about 55% with ethylene oxide,preferably in a concentration of about 100%. After being exposed toethylene oxide for about 6 hours, the products are aerated and kept at atemperature of about 35 to about 45° C. for about 22 hours, in order topermit the ethylene oxide to dissipate. The sterilized balloon productsare now ready for human use.

[0055] The sterilization process cannot, however, be conducted above theheat set temperature since this would relieve the orientation of thepolymer chains which was “locked” into place during heat set process.The sterilization process appears to be an important factor indetermining the final physical characteristics of the balloons andballoon catheters of this invention. Therefore, the novel sterilizationprocess is necessary to ensure a clinically useful and safe finishedballoon and balloon catheter with an overall advantageous combination ofphysical properties (i.e., distensibility, elastic stress response andwall tensile strength) superior to those exhibited by the “compliant”balloons of the prior art.

EXAMPLE 1

[0056] A parison was made from the polyurethane manufactured by The DowChemical Company and marketed under the trade name PELLETHANE 2363-75D.This material has a Shore Hardness of about 74 D, a specific gravity ofabout 1.21, a tensile strength of about 165,000 psi, a flexural modulusof about 190,000 psi, an ultimate tensile strength of about 6,980 psiand an ultimate elongation of about 250%. The parison was sealed at oneend while the other end was attached to the source of the pressurizedinflation fluid, in this example nitrogen gas. Clamps were attached toeach end of the parison. The mold was then heated to an operatingtemperature of about 90-100° C., while the parison was pressurized withnitrogen gas at about 290 psi and held for about 70 seconds.

[0057] The pressure was then relieved and the parison was subjected to aseries of radial expansion or “blow” cycles. During each radialexpansion or “blow” cycle, the parison was also axially stretched whilebeing pressured at about 290 psi for about 5 seconds. The pressure wasthen relieved, and the parison was subject to continued axial stretchingfor about 5 seconds. The parison was then subjected to another expansioncycle. After three expansion or blow cycles, the original outer diameterhad increased from 0.035 inches to 0.1181 inches.

[0058] The expanded parison was then pressurized to about 190 psi andwas subjected to a heat set step during which the expanded parison washeld for about 75 seconds at a temperature of about 110° C. Thepressurized balloon was then cooled to about 37° C. for about 30seconds. The pressure was then relieved and the balloon was heldvertically in the mold at about 37° C. for about 120 seconds to minimizeballoon curvature. The balloon was released from the clamps and removedfrom the mold. The balloon, having a nominal or rated diameter of 3.0mm, displayed an improved overall combination of distensibility, elasticstress response and strength when compared to “compliant” balloons ofthe art and was ready for attachment to a catheter.

EXAMPLE 2

[0059] The balloons formed following the process set forth in Example 1were placed in a sterilization chamber and kept at a temperature ofabout 40° C.±3° C. and a relative humidity of about 55% for about 15hours. The balloons are kept at a temperature of about 40° C.±3° C andwere then treated with 100% ethylene oxide. After being exposed to theethylene oxide for about 6 hours, the balloons were removed from thesterilization chamber and held at a temperature of about 40° C.±3° C.and ambient relative humidity for about 22 hours in order to dissipatethe ethylene oxide. At this point, the balloons were sterilized andready for human use.

EXAMPLE 3

[0060] The effect which the novel sterilization process of thisinvention has on the balloons formed using the balloon forming processcontemplated by this invention are demonstrated below. Balloons with anominal diameter of 3.0 mm were formed from polyurethane following theprocess described in Example 1. One group of balloons was subjected tothe sterilization process contemplated by this invention and describedpreviously in Example 2, sterilization process contemplated by thisinvention and described previously in Example 2, while the other groupof balloons were subjected to a sterilization process currently used inthe art.

[0061] In that sterilization process (referred to in this Example as“traditional sterilization process”), the balloons were preconditionedat a temperature of about 43° C. and a relative humidity of about 60%for about 24 hours. The balloons were then treated with about 12%ethylene oxide and 88% Freon™ at a temperature of about 54° C. Afterbeing treated with the ethylene oxide mixture for about 9 hours, theballoons are removed from the sterilization chamber and kept at atemperature of about 38° C. for about 22 hours.

[0062] The average wall tensile, burst pressure, elastic stress responseand distensibility (i.e., radial expansion) of both sets of balloonswere compared below. Average Wall Average Tensile Burst AverageSterilization Strength Pressure Elastic Stress Average Conditions (psi)(atm) Response Distensibility novel sterilization 16,297 22.0 3.38 9.4%conditions described in Example 2 traditional 14,497 22.6 10.29* 20.2%sterilization process

EXAMPLE 4

[0063] The following example demonstrates the importance of the heat setstep. Three dilatation balloons with a nominal or rated diameter of 3.0mm, were formed from polyurethane following the process described inExample 1. The average burst pressure, distensibility and wall tensilestrength of balloons formed using different heat set temperatures arecompared. The burst pressure and distensibility were determined at 37°C. Heat Set T Temperature Average Wall Tensile Average Burst Average (°C.) Strength (psi) Pressure (atm) Distensibility 160 14,712 12.8 10.26%132 23,364 20.6  5.81% 118 25,346 22.2  5.96%

EXAMPLE 5

[0064] The following example demonstrates the improved elastic stressresponse or “repeatability” which can be obtained by the balloons andballoon catheters formed following the process contemplated by thisinvention. In this example, dilatation balloons with a nominal or rateddiameter of 3.0 mm were formed from polyurethane following the processdescribed in Example 1. A number of polyurethane balloons weresterilized following the process previously described in Example 3(referred to as “traditional sterilization” in this Example). Anothergroup of polyurethane balloons were sterilized using the novelsterilization contemplated by this invention and previously described inExample 2. The elastic stress response of these polyurethanes balloonswere compared with the elastic stress response of other sterilized 3.0mm balloons known in the art. Average Average Diameter at Diameter at 5Bars Averag Initial 5 Bar After A Single Elastic Stress BalloonInflation Inflation to 10 Bars Response Polyurethane 2.96 3.06 3.38(sterilization described in Example 2) Polyurethane 2.72 3.00 10.29 (traditional sterilization) Polyethylene 3.02 3.04 0.66 terephthalateCross-linked 2.98 3.11 4.36 polyethylene Cross-linked 2.93 3.19 8.87polyolefin-ionomer

EXAMPLE 6

[0065] The following example demonstrates the improved overallcombination of distensibility, elastic stress response and wall tensilestrength obtained by forming balloons by using the process of thisinvention. Balloons with a nominal or rated diameter of 3.0 mm wereformed from polyurethane following the process described in Example 1.The average elastic stress response, distensibility and wall tensilestrength of those polyurethane balloons are compared with properties ofother 3.0 mm balloons of the art. Average Wall Average Elastic AverageTensile Balloon Stress Response Distensibility Strength (psi)Polyurethane 3.38 9.4% 16,297 Polyethylene 0.66 3.26% 62,081terephthalate Cross-linked 4.36 9.67% 8,868 polyethylene Cross-linked8.87 14.64% 6,793 polyolefin-ionomer

1. A balloon characterized by an improved overall combination ofdistensibility, elastic stress response and wall tensile strength madeby the process comprising: a. providing a parison of a block copolymerhaving regions of inter-molecular chain interaction separated by regionsin which those individual portions of the polymer chains have theability to uncoil, said parison having a predetermined original outerdiameter, a predetermined wall thickness and a predetermined length; b.subjecting said parison to at least one axial stretch step and at leastone radial expansion step at temperature T₁ which is below the meltingtemperature of said block copolymer to increase the diameter and lengthof said parison to at least 3 times the original diameter and 2 timesthe original length and to decrease the original wall thickness to atleast 20% of the original wall thickness to form an expanded parison;and c. heating said expanded parison to a temperature of T₂ which isabove T₁ but below the melting temperature of said block copolymer. 2.The balloon according to claim 1 wherein said radial expansion step isconducted while said parison is simultaneously subjected to said axialstretch step.
 3. The balloon according to claim 1 wherein said axialstretch and radial expansion steps are conducted at temperature T₁ whichis greater than the glass transition temperature of said blockcopolymer.
 4. A balloon according to claim 1 wherein said blockcopolymer is selected from the group consisting of polyester blockcopolymers, polyamide block copolymers, polyurethane block copolymers, amixture of nylon and polyamide block copolymers and a mixture ofpolyethylene terephthalate and polyester block copolymers.
 5. A balloonaccording to claim 1 wherein said balloon has a distensibility of about5 to about 20%, an elastic stress response not greater than about 5.00,and a wall tensile strength greater than about 14,000 psi.
 6. A balloonaccording to claim 1 wherein said balloon has a distensibility of about6 to about 17%, an elastic stress response of about 0.75 to about 4.00and a wall tensile strength of about 16,000 to about 30,000 psi.
 7. Aballoon according to claim 1 wherein said block copolymer is apolyurethane having a Shore Hardness of about 74 D, a specific gravityof about 1.21, a tensile modulus of about 165,000 psi, a flexual modulusof about 190,000 psi, an ultimate tensile strength of about 6,980 psiand an ultimate elongation of about 250%.
 8. A balloon according toclaim 6 wherein T₁ is about 90-100° C. and T₂ is about 110-120° C.
 9. Aprocess of forming a balloon characterized by an improved overallcombination of distensibility, elastic stress response and wall tensilestrength comprising: a. providing a parison of a block copolymer havingregions of inter-molecular chain interaction separated by regions inwhich those individual polymer portion of chains have the ability touncoil, said parison having a predetermined original outer diameter, apredetermined wall thickness and a predetermined length; b. subjectingsaid parison to at least one axial stretch step and at least one radialexpansion step at temperature T₁ which is below the melting temperatureof said block copolymer to increase the diameter and length of saidparison to at least 3 times the original diameter and 2 times theoriginal length and to decrease the original wall thickness to at least20% of the original wall thickness to form an expanded parison; and c.heating said expanded parison to a temperature of T₂ which is above T₁but below the melting temperature of said block copolymer.
 10. Theprocess according to claim 9 wherein said radial expansion step isconducted while said parison is simultaneously subjected to said axialstretch step.
 11. The process according to claim 9 wherein said axialstretch and radial expansion steps are conducted at temperature T₁ whichis greater than the glass transition temperature of said blockcopolymer.
 12. A process according to claim 9 wherein said blockcopolymer is selected from the group consisting of polyester blockcopolymers, polyamide block copolymers, polyurethane block copolymers, amixture of nylon and polyamide block copolymers and a mixture ofpolyethylene terephthalate and polyester block copolymers.
 13. A processaccording to claim 9 wherein said balloon formed has a distensibility ofabout 5 to about 20%, an elastic stress response of not greater thanabout 5.00 and a wall tensile strength greater than about 14,000 psi.14. A process according to claim 9 wherein the balloon formed has adistensibility of about 6 to about 17%, an elastic stress response ofabout 0.75 to about 4.00 and a wall tensile strength of about 16,000 toabout 30,000 psi.
 15. A process according to claim 9 wherein said blockcopolymer is a polyurethane having a Shore Hardness of about 74 D, aspecific gravity of about 1.21, a tensile modulus of about 165,000 psi,a flexual modulus of about 190,000 psi, an ultimate tensile strength ofabout 6,980 psi and an ultimate elongation of about 250%.
 16. A ballooncatheter comprising the balloon of claim
 1. 17. A process forsterilizing balloons and balloon catheters comprising: a. subjectingsaid balloons and balloon catheters to a temperature of about to about45° C. and a relative humidity of about 55% for about 15 hours; b.treating said balloons and balloon catheters at a temperature of about35 to about 45° C. and a relative humidity of about 55% with ethyleneoxide for about 15 hours; and c. discontinuing treatment with ethyleneoxide and subjecting said balloons and balloon catheters to atemperature of about 35 to about 45° C. for about 22 hours.